CN1313469C - Novel derivative of flavone c-glycoside and composition containing the same - Google Patents

Novel derivative of flavone c-glycoside and composition containing the same Download PDF

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CN1313469C
CN1313469C CNB038181061A CN03818106A CN1313469C CN 1313469 C CN1313469 C CN 1313469C CN B038181061 A CNB038181061 A CN B038181061A CN 03818106 A CN03818106 A CN 03818106A CN 1313469 C CN1313469 C CN 1313469C
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food
flavone
salt
compound
glycoside derivatives
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CN1671713A (en
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石仓义之
辻邦郎
糠谷东雄
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Suntory Holdings Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
    • C07D493/14—Ortho-condensed systems
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair

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Abstract

The present invention relates to novel flavone C-glycoside derivatives or salts thereof, especially those showing an anti-allergic effect, and compositions containing them. Recently, cases of allergic diseases, especially pollenosis and atopic dermatitis have increased to such a degree that they have become a social problem. Flavones and their glycosides have been reported to have the effect of inhibiting histamine release from mast cells or an immunosuppressive effect and expected for application as allergy therapies. However, most flavones exhibit their effects only at high doses, so that effective compounds at lower doses are highly desired. The present invention provides novel components capable of treating allergic diseases at low doses and compositions containing them.

Description

The derivative of flavone C glycoside and the composition that contains it
Technical field
The present invention relates to demonstrate especially the antiallergic property effect flavone C glycoside new derivatives or its salt and contain its composition.
Background technology
In recent years, shown that according to various epidemiology surveys anaphylactic disease is increasing.Particularly the increase of pollinosis and atopic dermatitis is remarkable, even has become social concern.These variations of the variation of the increase of anaphylactin and topsoil and food additives, food habits around our environment inferred be the irritated reason that increases (her rattan, sum up clinical, 41: 3099 (1992)).The methods of treatment of anaphylactic disease is carried out is at first will removing or not absorb as the anaphylactin of reason, according to pathogenetic pharmacotherapy of degree He each disease of symptom.Anaphylaxis because of as the difference of the immunoglobulin (Ig) of its reason, the immunocyte that relates to by for being four types on I type～IV type.I type～III type allergy relates to the immune response of humoral antibody, because anaphylaxis occurs rapidly, therefore is also referred to as immediate hypersensitivity, IV type allergy and irrelevant antibody, be the cellular immunity reaction relevant with primed lymphocyte, be also referred to as delayed allergy (Fu Gang, sum up clinical, 41: 3103 (1992)).
In these anaphylaxis, pollinosis is considered to relevant with I type and type iv allergic reaction with atopic dermatitis, and antihistaminic, alkaline anti-allergic agent or steroid dose etc. are used in its treatment.
On the other hand, also applied for and the patent of having utilized the L-Epicatechin gallate anti-allergic agent in oolong tea extract or the tea (spy opens flat 10-077231, the spy opens flat 10-175874, patent 3023962 etc.).In addition, report shows that flavones and its glucosides have free effect and immunosuppressive action in the histamine release from mast cells of inhibition, is subjected to expectation (Kubo M.etal, Chem.Pharm.Bull. as the application of irritated curative 32: 5051 (1984)).But nearly all flavones shows the consumption height of its effect, eager compound of wishing with lower consumption display effect.
Summary of the invention
The object of the present invention is to provide separating substances, the evaluation that will have anti-allergic effects, providing can be with the novel components and the composition that contains them of low consumption treatment anaphylactic disease.
Present inventors are in order to solve above-mentioned problem, be primarily focused on the anti-allergic effects of oolong tea, antianaphylaxis components in the oolong tea has been carried out detailed research, it found that: the derivative of novel flavone C glycoside or its salt pair 2, the ear swelling that 4-dinitrobenzene fluorobenzene (DNFB) brings out form inhibited and have an inhibition effect to histamine is free from the abdominal cavity mastocyte.In addition, discovery can be with them as the effective constituent utilization in medical composition, food compositions or the makeup, thereby has finished the present invention.
Description of drawings
Fig. 1 is illustrated in and carries out in the experimental example 1, with the administered dose of compound of the present invention (1) be 0.2,1.0 and 5.0 μ g/kg three kinds of concentration and when giving 0.5% Xylo-Mucine/0.01N hydrochloric acid in contrast for the graphic representation of the difference of the inhibition effect of Mice Auricle contact dermatitis.
Fig. 2 is illustrated in and carries out in the experimental example 2, with the administered dose of compound of the present invention (2) be 1.0,10 and 100 μ g/kg three kinds of concentration and when giving 0.5% Xylo-Mucine/0.01N hydrochloric acid in contrast for the graphic representation of the difference of the inhibition effect of Mice Auricle contact dermatitis.
The structure of Fig. 3 representation class flavones.
Embodiment
As mentioned above, the present inventor is in order to solve above-mentioned problem, to concentrate on the anti-allergic effects of oolong tea, antianaphylaxis components in the oolong tea has been carried out detailed research, it found that: the derivative of novel flavone C glycoside or its salt pair 2, the ear swelling that 4-dinitrobenzene fluorobenzene (DNFB) brings out form inhibited and have an inhibition effect to histamine is free from the abdominal cavity mastocyte.In addition, discovery can be with them as the effective constituent utilization in medical composition, food compositions or the makeup, thereby has finished the present invention.
Therefore, the present invention relates to derivative or its salt of the flavone C glycoside shown in the formula (1).
Figure C0381810600051
In addition, the present invention relates to derivative or its salt of the flavone C glycoside shown in the formula (2).
Figure C0381810600061
The present invention relates to preventing and/or treating of anaphylactic disease and use medical composition, it contains the derivative of above-mentioned flavone C glycoside or at least a kind of its salt.In addition, the present invention relates to medical composition, wherein, this anaphylactic disease is at least a disease that is selected from atopic dermatitis, contact dermatitis, pollinosis.
The present invention relates to food compositions, it contains the derivative (1) of above-mentioned flavone C glycoside or (2) or its salt at least a kind.In more detail, the present invention relates to food compositions, wherein, this food compositions is as the beverage of specific food for health care, food of special nutrients, dietary supplement or other nutritional drink, healthy beverage, healthy tea, Other Drinks.In addition, the present invention relates to food compositions, wherein, this food compositions is cake class, bread, wheaten food class, soyabean processing product, milk-product, egg processed goods, the flesh of fish is blended prepared food, grease or the food flavouring that adds other material and make.
In addition, the present invention relates to the material of making up, it contains the derivative (1) of above-mentioned flavone C glycoside or (2) or its salt at least a kind.In addition, the present invention relates to makeup, wherein, this material of making up is skin care product, makeup, hair cosmetic material or bathing material.
The derivative of the flavone C glycoside of formula involved in the present invention (1) and/or formula (2) or its salt, can be for example, with tealeaves is raw material, by implement heating and adopt that solvent carries out extracting, concentrates, general refining means (for example, classification or chromatography) of chemical separation such as refining and obtaining.
The tealeaves that uses when making can use the leaf of tea tree (Camellia sinensis) and/or with the tealeaves after its processing.Especially preferably use oolong tea.So-called oolong tea is meant with Fujian China province, Guangdong Province or Taiwan etc. to be the original semi-fermented tea of China on main product ground.
What be used for that the solvent of stripping can be for water solvent and/or organic solvent is any, preferably uses water solvent.Water solvent preferably water, ethanol or methyl alcohol etc.Can for water separately or the mixing solutions arbitrarily of lower alcohols such as water and methyl alcohol, ethanol.
The ratio of oolong tea and solvent also is not particularly limited during extracting, and with respect to oolong tea 1 weight part, solvent is 2～1000 weight parts, considers extraction procedure, efficient aspect, preferred especially 5～100 weight parts.
In addition,, then be not particularly limited if the temperature during stripping is lower than boiling point than the fusing point height of solvent, but if water, preferred 10 ℃～100 ℃, if ethanol and methyl alcohol, preferred 10 ℃～40 ℃.The extracting time is preferably 10 seconds～24 hours scope.
As the refining means of chemical separation, can use as the refining normally used method of means of chemical separation, can use for example liquid-liquid separation, tlc, adsorpting column chromatogram method, partition column chromatography, gel-filtration column chromatography, ion exchange column chromatography method, electrophoresis or high performance liquid chromatography etc.In addition, also can be as required with these separation and purification means combinations, be high purity with derivative or its salt refining of the flavone C glycoside of formula involved in the present invention (1) and formula (2).
Therefore the derivative of the flavone C glycoside of formula involved in the present invention (1) and formula (2) or its salt can use in various uses such as medicine, foods and cosmetics owing to show anti-allergic effects.As medicine, the ear swelling that the compound or its salt of formula (1) and/or (2) brings out DNFB forms and shows restraining effect and to the free restraining effect that shows of histamine, so, can be used in particular for the therapeutic purpose of atopic dermatitis, contact dermatitis and pollinosis as anti-allergic agent.As food, be purpose with the mitigation and the prevention of the symptom of atopic dermatitis, contact dermatitis and pollinosis, can be used as food additives and be matched with in specific food for health care, food of special nutrients, dietary supplement, the heath food etc.Food as adding object can be various food.As beverage, can be matched with in the beverage of specific food for health care, food of special nutrients, dietary supplement and other nutritional drinks, healthy beverage, various healthy tea, Other Drinks etc.As other food, can enumerate cake class, bread, wheaten food class, soyabean processing product, milk-product, egg processed goods, the flesh of fish is blended the prepared food that adds other material and make, grease, food flavouring etc.As makeup, be purpose with the mitigation and the prevention of the symptom of atopic dermatitis, contact dermatitis and pollinosis, can be in skin care product, foundation cream and makeup etc. the compound or its salt of adding type (1) and/or formula (2).
About medicine, can be directly or dilution such as water, the compound or its salt of per os giving construction (1) and/or formula (2).Or by it is modulated with known pharmaceutical carrier preparationization.For example,, or be processed into medicinal extract, powder etc., cooperate, give as per os solid preparations such as tablet, capsule, granule, powders with the carrier that pharmaceutically allows with the aqueous preparations of per os such as compound or its salt system pulping agent of formula (1) and/or formula (2).As the carrier that pharmaceutically allows, can use habitual various organic or inorganic carrier substance as the preparation starting material, as the vehicle in the solid preparation, lubricant, wedding agent, disintegrating agent, cooperations such as the solvent in the aqueous preparation, vehicle, suspension agent, wedding agent.In addition, also can use preparation additives such as sanitas, antioxidant, colouring matter, sweeting agent as required.
As the preferred example of vehicle, can enumerate for example lactose, white sugar, D-mannitol, starch, crystalline cellulose, light silicon anhydride etc.As the preferred example of lubricant, can enumerate for example Magnesium Stearate, calcium stearate, talcum, colloid silica etc.As the preferred example of wedding agent, can enumerate for example cellulose-binding, white sugar, D-mannitol, dextrin, hydroxypropylcellulose, Vltra tears, Polyvinylpyrolidone (PVP) etc.As the preferred example of disintegrating agent, can enumerate for example polyoxyethylene glycol, propylene glycol, D-mannitol, peruscabin, ethanol, Trisaminomethane, cholesterol, trolamine, yellow soda ash, Trisodium Citrate etc.As the preferred example of liquor, can enumerate for example Purified Water, alcohol, propylene glycol etc.As the preferred example of suspension agent, can enumerate for example tensio-active agents such as stearic acid thanomin, Sodium Lauryl Sulphate BP/USP, lauryl alanine, Yelkin TTS, Zephiran chloride, benzethonium chloride, Zerol; And hydrophilic macromolecules such as polyvinyl alcohol, Polyvinylpyrolidone (PVP), Xylo-Mucine, methylcellulose gum, Walocel MT 20.000PV, Natvosol, hydroxypropylcellulose for example.As the preference of sanitas, can enumerate for example parabens, butylene-chlorohydrin, benzylalcohol, phenylethyl alcohol, dehydroacetic acid (DHA), Sorbic Acid etc.As the preference of oxidation inhibitor, can enumerate for example sulphite, xitix etc.
As formulation, it depends on the kind of disease and degree etc., for example, as being suitable for the formulation that per os, non-per os or intranasal give, can enumerate tablet or coated tablet, Sublingual tablet, gelatine capsule agent, lozenge (troche), suppository, paste, ointment, skin with gelifying agent etc.In addition, effectively consumption because of the kind of patient's age and body weight, disease and severity and give by way of changing.The unit consumption generally is to give 1～3 time in per 24 hours, gives the scope of 0.0001～100mg/kg at every turn.
About food, can directly or be processed into medicinal extract, powder etc., with the form giving construction (1) of ingesta and/or the compound or its salt of formula (2).In addition, can cooperate with the carrier that allows in the ingesta starting material of general use and the ingesta manufacturing, as beverage, cake class, bread, wheaten food class, soyabean processing product, milk-product, egg processed goods, the flesh of fish is blended prepared food, grease or the food flavouring etc. that add other material and make provide.
In the present invention, so-called beverage is meant oolong tea beverage, with drinks such as other tea drink blended tea drink, soda pop, fruit nectar, lactobacillus drink, sports beverages, soymilk and grape wine, liquor, whisky, pure mellow wines etc.
In the present invention, so-called cake class is meant Biscuits, chocolate-like, candy class, chewing gum class, fast food cake class, fried cake, Western-style fresh cake, Japanese cake, ice cream class, fruit jelly etc.
Comprise bean curd etc. in the soyabean processing product, comprise yogourt, butter etc. in the milk-product.Comprise scrambled egg, bowl Steamed Egg Custard etc. in the egg processed goods, meat is blended to add in the prepared food that other material makes comprise breaded fish stick etc.Comprise seasonings (soy sauce), seasonings (spices), mayonnaise in the food flavouring, be sprinkling upon food flavouring (fish meal, laver end etc.) of eating on the meal etc.They can adopt the usual method manufacturing.
As the carrier that allows in the ingesta manufacturing, can enumerate sweet taste material such as granulated sugar, glucose, fructose, isomerization liquid sugar, oligofructose, aspartame, Sorbitol Powder, sweet Stevia; Cabbage pigment, uva skin pigment, connect colouring matters such as fruit tree pigment, caramel colorant, flower of Capa Jasmine pigment, corn pigment, safran, Radix Dauci Sativae; Pectin decomposer, phenylformic acid, Sorbic Acid, parabens, potassium sorbate etc. are preserved material; Thickeners such as sodiun alginate, Protanal Ester SD-LB, glycolic cellulose calcium, glycolic cellulose sodium; Oxidation inhibitor such as L-xitix, tocopherol, saccharosonic acid, violaguercitrin; Chromogenic reagents such as ferrous sulfate, Sodium Nitrite, saltpetre; SYNTHETIC OPTICAL WHITNER such as sodium bisulfite, Potassium metbisulphite; Quality retention agents such as propylene glycol; Quality improving agent such as L-cysteine hydrochloride, stearyl calcium lactate; Swelling agents such as ammonium chloride, d-tartarus, volatile salt, salt of wormwood, sodium bicarbonate, alum; Emulsifying agents such as Yelkin TTS, sphingolipid, vegetalitas cholesterol, soybean saponin, sodiun alginate, Protanal Ester SD-LB, sodium caseinate food grade, glycerol fatty acid ester, sucrose fatty ester, sorbitan fatty(acid)ester; Emulsion stabilizers such as sodium chondroitin sulfate; Lemon oil, Oil of Eucalyptus, spearmint oil, vanilla concrete, orange oil, garlic oil, methyl aceto acetate, aubepine, vanirone, styracin, geraniol acetate, citral, vanillin food grade,1000.000000ine mesh, butyl butyrate, ester class are waited spices; L-xitix, altheine, L-L-Ala, inositol, L-glutaminate, carotene, tocopherol, vitamin A, folic acid, ironic citrate, heme iron, do not calcine reinforcers such as calcium; Wheat-flour modifying agents such as benzoyl peroxide, ammonium persulphate, dioxide peroxide; Sterilization material such as chlorinated lime, hydrogen peroxide, hypochlorous acid; Anti-adhesive agents such as the basis agent of chewing gums such as ethanoyl ricinolic acid methyl esters, ester gum, vinyl acetate resin, polyisobutene, polybutene, D-mannitol; Caking agents such as acidic sodium pyrophosphate, potassium pyrophosphate, trisodium phosphate; Acid flavorings such as hexanodioic acid, citric acid, glyconic acid, succsinic acid, d-tartrate, lactic acid, d1-oxysuccinic acid; Sea-food extract, yeast extract, Seaweed Extract, soy sauce, tomato-sauce, meat extract, cooking wine, jam, boil and food flavourings such as exsiccant stripped tuna meat, L-Sodium L-aspartate, DL-L-Ala, L-arginine, L-glutaminate, 5 '-inosine acid disodium, trisodium citrate, L-L-glutamic acid, L-Sodium Glutamate, succsinic acid, L-tartrate, Sodium.alpha.-hydroxypropionate etc.
The compound or its salt of formula provided by the invention (1) and/or formula (2) can be directly or dilution such as water; or concentrate; or powdered or granulating; by cooperating, apply forms such as (pap) agent, basting agent, lotion and provide as aerosol, liquor, extractum, suspension agent, emulsion, ointment, mud with known carrier.But perhaps suitably select to be used for the water composition, tensio-active agent, oiliness composition solvation, wetting Agent for Printing Inks, powder composition, alcohols, pH regulator agent, sanitas, oxidation inhibitor, tackifier, pigment, pigment, spices etc. of known makeup, accurate pharmaceuticals, pharmaceuticals as required and modulate.As external composition for skin, also can become formulations such as lotion shape, gel, emulsion, ointment.
In the present invention, so-called skin care product are meant astringent classes such as flexibility astringent, convergency astringent, cream classes such as soothing cream, humidification cream, massage cream, emulsion classes such as moisturizer, nutritional emulsions, cleaning emulsion etc.
The so-called material of making up is meant the material that washes one's face, skin detergent, foundation cream, eye shadow, rouge, lipstick etc.
So-called hair cosmetics is meant shampoo, rinsing liquid, hair-care agent, hair-cream, hair mousse, hair tonic, hair growth promoter, educates mao agent etc.So-called bathing agent is meant bathing oil, bath salt, bathing foam etc.
About the food and the material of making up, its use level also is not particularly limited, and generally is scaled the drying solid composition, is 0.0001～100 weight %, is preferably 0.001～50 weight % especially.
Enumerate experimental example and embodiment is described in more detail the present invention, but scope of the present invention is not restricted to these experimental examples and embodiment.
Embodiment
Embodiment 1: Production Example
Use hot water 100L that the frozen fresh oolong tea 5.0kg that is produced from Chinese Fujian Province is carried out extracting, in the post of the synthetic adsorbent (DIAION HP-21, Mitsubishi Chemical society system) that putting packs into after cold has filled 30L, in the post of the synthetic adsorbent (DIAION HP-20, Mitsubishi Chemical society system) that will not have the adsorption stage branch to pack into again to have filled 30L, increase the content of ethanol in turn with respect to water, make its outflow (average out to 60L respectively), obtain 4 fractions [alcohol concn=0% (OHF3N), 20% (OHF4N), 40% (OHF5N), 99.5% (OHF6N)].
The ear swelling that in these 4 fractions DNFB brought out formed have that the strongest inhibiting OHF3N fraction concentrates, lyophilize (517g), water-propyl carbinol carries out flow distribution (n=7) again, the concentrating under reduced pressure thing (2.1g) of the fraction of transfer number 7 times packed into filled in the post of Sephadex LH-20 (Pharmacia Biotech society system), use the methyl alcohol stripping, collect the fraction of Kd value 1.9～2.2.With HPLC this concentrating under reduced pressure thing is separated.Post uses SENSHU PAK DIOL-1251 (SENSHU chemistry society system, 4.6 * 250mm), mobile phase is used hexane: methyl alcohol: the solvent of tetrahydrofuran (THF)=50: 35: 15, make its stripping with flow velocity 1ml/min (30 ℃), divide the peak (UV280nm) of the stripping when staying 5.8 minutes time of going bail for.Behind the concentrating under reduced pressure, (YMC society system, 4.6 * 150mm) HPLC make with extra care by having adopted YMC-Pack ODS-A.After branch is got,, obtain the pale yellow powder of 980 μ g by concentrating under reduced pressure.
Resolve the result's (table 1 and table 2) who carries out structure elucidation with spectrum such as NMR, MS and X ray: this compound is accredited as the compound [compound (1)] of 1 OH intramolecular dehydration condensation of 7 the OH of different vitexin (Isovitexin) (with reference to Fig. 3) of formula (1) and sugar chain.
Table 1 compound (1) by 1H-NMR and 13The structure that C-NMR measures
Part Aglycon Sugar
C H C H
2 3 4 5 6 7 8 9 10 1’ 2’ 3’ 4’ 5’ 6’ 168.1 102.9 184.8 168.7 112.6 166.5 91.8 161.2 107.9 119.3 130.2 119.3 168.1 119.3 130.2 6.58s 6.64s 7.80d 6.80d 6.80d 7.80d 1″ 2″ 3″ 4″ 5″ 6″ 74.6 89.0 73.9 69.8 80.6 63.5 5.21d 4.67t 3.98t 3.58t 3.33m 3.62m，3.83m
Compound (1) by 1H-NMR and 13The structure (ppm.in CD3OD) that C-NMR measures
Table 2 compound (1) is resolved the structure of measuring by X ray
Crystal size lattice parameter space group Z value DcalcThe R value 0.10×0.05×0.20mm a＝10.811(6) b＝26.270(6) c＝6.905(1) V＝1961.0(9) 3 P2 12 12 1 4 1.403g/cm 3 0.078
OHF3N fraction (517g) water-propyl carbinol in the treating process of compound (1) is carried out flow distribution (n=7), the concentrating under reduced pressure thing (2.1g) of the fraction of transfer number 7 times packed into filled in the post of Sephadex LH-20 (Pharmacia Biotech society system), use the methyl alcohol stripping, collect the fraction of Kd value 1.6～1.9.With HPLC this concentrating under reduced pressure thing is separated.Post uses SENSHUPAK DIOL-1251 (SENSHU chemistry society system, 4.6 * 250mm), mobile phase is used hexane: methane: the solvent of tetrahydrofuran (THF)=50: 35: 15, make its stripping with flow velocity 1ml/min (30 ℃), divide the peak (UV280nm) of the stripping when staying 5.8 minutes time of going bail for.Behind the concentrating under reduced pressure, (YMC society system, 4.6 * 150mm) HPLC make with extra care by having adopted YMC-Pack ODS-A.After branch is got,, obtain the pale yellow powder of 147 μ g by concentrating under reduced pressure.
Resolve the result's (table 3 and table 4) who carries out structure elucidation with wave spectrum such as NMR, MS and X ray: this compound is accredited as the compound [compound (2)] of 1 OH intramolecular dehydration condensation of 7 the OH of vitexin (Vitexin) (with reference to Fig. 3) of formula (2) and sugar chain.
Table 3 compound (2) by 1H-NMR and 13The structure that C-NMR measures
Part Aglycon Sugar
C H C H
2 3 4 5 6 7 8 9 10 1’ 2’ 3’ 4’ 5’ 6’ 166.8 104.3 184.4 166.2 96.3 168.9 108.5 155.1 106.7 125.0 130.2 118.0 164.9 118.0 130.2 6.66s 6.39s 7.90d 6.93d 6.93d 7.90d 1″ 2″ 3″ 4″ 5″ 6″ 75.1 89.1 73.8 69.8 80.5 63.4 5.47d 4.78t 4.05t 3.62t 3.47m 3.65m，3.87m
Compound (2) by 1H-NMR and 13Structure (the ppm.in CD that C-NMR measures 3OD)
Table 4 compound (2) is resolved the structure of measuring by X ray
Crystal size lattice parameter space group Z value DcalcThe R value 0.03×0.10×0.30mm a＝9.785(2) b＝19.700(5) c＝4.9357(8) V＝950.1(3) 3 P2 1 2 1.560g/cm 3 0.058
Experimental example 1: to the inhibition effect of rat auricle contact dermatitis
Using animal is mouse for the ICR in 7 ages in week of buying from Japanese Network レ ア (strain), raised for 1 week in advance after, be used for experiment.The yellow powder [compound (1)] of preparation among the embodiment 1 is suspended in 0.5% Xylo-Mucine/0.01N hydrochloric acid, and the modulation administered dose is 3 kinds of concentration samples of 0.2,1.0 and 5.0 μ g/kg, makes administered dose reach 10ml/kg.Mouse is 1 group 6, to 2 of back subcutaneous injection 1%, and 4-dinitrobenzene fluorobenzene (DNFB) ethanolic soln 100 μ l, its infection of chien shih during with 5 days.Made the generation auricle contact dermatitis at the wide coating of auris dextra 1%DNFB olive oil solution on the 6th day.After 24 hours, two ears are bored a hole gravimetry with the puncher of diameter 8mm.From primary infection the day before yesterday to causing that the per os that carries out compound (1) 7 days of edema same day continuously gives.Group gives 0.5% Xylo-Mucine/0.01N hydrochloric acid in contrast.Experimental result represents with respect to the mean value and the standard deviation of the edema rate of left auricle that with the auris dextra exterior feature t-check of Student is used in the meaningful difference check between group.It the results are shown in Fig. 1.As seen from Figure 1, with the control group that gives 0.5% Xylo-Mucine/0.01N hydrochloric acid relatively, in 1.0 and 5.0 μ g/kg of compound (1) organized, the edema that DNFB causes had obtained the inhibition had a mind to.
Experimental example 2: to the inhibition effect of rat auricle contact dermatitis
Using animal is mouse for the ICR in 7 ages in week of buying from Japanese Network レ ア (strain), raised for 1 week in advance after, be used for experiment.The yellow powder [compound (2)] of preparation among the embodiment 1 is suspended in 0.5% Xylo-Mucine/0.01N hydrochloric acid, and the modulation administered dose is 3 kinds of concentration samples of 1.0,10 and 100 μ g/kg, makes administered dose reach 10ml/kg.Mouse is 1 group 6, to 2 of back subcutaneous injection 1%, and 4-dinitrobenzene fluorobenzene (DNFB) ethanolic soln 100 μ l, its infection of chien shih during with 5 days.Made the generation auricle contact dermatitis at the wide coating of auris dextra 1%DNFB olive oil solution on the 6th day.After 24 hours, two ears are bored a hole gravimetry with the puncher of diameter 8mm.From primary infection the day before yesterday to causing that the per os that carries out compound (2) 7 days of edema same day continuously gives.Group gives 0.5% Xylo-Mucine/0.01N hydrochloric acid in contrast.Experimental result represents with respect to the mean value and the standard deviation of the edema rate of left auricle that with the auris dextra exterior feature the poor check of having a mind between group uses the t-of Student to check.It the results are shown in Fig. 2.As seen from Figure 2, with the control group that gives 0.5% Xylo-Mucine/0.01N hydrochloric acid relatively, in compound (2) 100 μ g/kg organized, the edema that DNFB causes had obtained the inhibition had a mind to.
Experimental example 3: suppress effect for histamine free from the abdominal cavity mastocyte
Using animal is rat for the Wistar in 7 ages in week of buying from Japanese Network レ ア (strain), raised for 1 week in advance after, be used for experiment.After under etherization Wistar being the rat sacrificed by decapitation, inject Tyrode liquid at intraperitoneal.Adopt conventional process that mastocyte is separated, be suspended in the Tyrode liquid that contains 0.1% bovine serum albumin (BSA) and make it to reach 1～3 * 10 8Cell/ml, the modulation mastocyte liquid that swims.Add above-mentioned mastocyte and swim in the liquid being dissolved in the compound (1) of 50% methyl alcohol or compound (2), under 37 ℃, carry out insulation in 5 minutes.Then, add Compound48/80, be incubated 10 minutes down at 37 ℃, after ice-cold, to the supernatant liquor of centrifugation method [J.Med.Sci. according to Onda etc., 27,93-97 (1978)], measure free histamine amount by the Liquid Chromatograph of method (post-column method) behind the post that has used o-phthalaldehyde(OPA) (OPA).Experimental result is by the histamine free amount with respect to only with solvent treatment the time, and the inhibiting rate that dissociates of the histamine when handling with test portion is represented.It the results are shown in table 5.
The table 5 histamine inhibition test result that dissociates
Test portion Concentration (μ g/ml) The histamine inhibiting rate (%) that dissociates
Compound (1) 5.0 62.3
Compound (2) 50.0 51.2
Embodiment 2: compare with the effect of sterides compound agent and other flavonoids
Use the method identical with embodiment 1 and embodiment 2, the restraining effect of the ear swelling formation that the agent of adrenal cortex steroide and multiple flavonoid (Fig. 3) are brought out DNFB and compound (1) and compound (2) compare.The administered dose that experimental result uses the ear swelling that DNFB is brought out to form inhibition 50% is represented.It the results are shown in table 6.
With adrenocorticosteriodpreparation preparation agent or other flavonoids relatively, the giving of compound (1) and compound (2) gives minute quantity and just demonstrates restraining effect to ear swelling formation.
Table 6 ear swelling forms inhibiting evaluation result
Administered dose (mg/kg p.O.) with ear swelling inhibition 50%
Compound (1) 0.05
Compound (2) 0.17
Dexamethasone 1.5
Apigenin (Apigenin) 247
Vitexin 103
Rhamnosyl vitexin 146
Xanthaurine (Quercetin) 265
Violaguercitrin 123
Embodiment 3: the Production Example of tablet
Compound (1) 150g of preparation among the embodiment 1 is mixed with the lactose and the Magnesium Stearate 5g of equivalent, this mixture is beaten sheet, make the tablet of diameter 10mm, weight 300mg with single-shot formula tablet machine.
Embodiment 4: the Production Example of granule
The tablet of preparation among the embodiment 2 is pulverized, granulates, sieved, obtain 20-50 purpose granule.
Embodiment 5: the Production Example of sugar
Use following material, according to the usual method manufacturing.
Powder Sorbitol Powder 99.7g
Spices 0.2g
Compound (1) 0.05g
Sorbitol Powder kind 0.05g
Total amount 100g
Embodiment 6: the Production Example of chewing gum
Use following material, according to the usual method manufacturing.
Initial rubber 20g
Lime carbonate 2g
Stevioside (stevioside) 0.1g
Compound (1) 0.05g
Lactose 76.85g
Spices 1g
Total amount 100g
Embodiment 7: the Production Example of orange juice
Use following material, according to the usual method manufacturing.
Freeze concentration orange fruit juice 5g
Fructose-glucose syrup 10g
Citric acid 0.2g
L-xitix 0.02g
Compound (1) 0.05g
Spices 0.2g
Pigment 0.1g
Water residual quantity
Total amount 100g
Embodiment 8: the Production Example of fruit jelly
Use following material, according to the usual method manufacturing.
Granulated sugar 500g
Malt sugar 500g
Pectin 13g
Citric acid 4g
Trisodium Citrate 1.5g
Spices 1g
Food dye 0.2g
Compound (1) 0.5g
Granulated sugar 20g is mixed among the pectin 13g, adds entry 330ml, make its dissolving evenly.Add citric acid and Trisodium Citrate again, make its boiling.After wherein add malt sugar, being heated to 100 ℃, add remaining granulated sugar, be warmed up to 109 ℃.After leaving standstill several minutes, adding compound (1), spices and pigment also stirs, and is filled in the starch mould, dry more than 10 hours below 50 ℃, obtains fruit jelly.
Embodiment 9: the Production Example of breaded fish stick
Use following material, according to the usual method manufacturing.
The meat stuffing 100g of cod
Salt 20g
Food flavouring 2g
Egg white 10g
Compound (1) 0.5g
In the meat stuffing of cod, add salt, food flavouring and compound (1) and mix, the slaking aftershaping, boiling in being heated to about 90～95 ℃ steaming device is in advance put coldly then, obtains breaded fish stick.
Embodiment 10: the Production Example of soothing cream
Use following material, according to the usual method manufacturing.
Beeswax 2.0g
Stearyl alcohol 5.0g
Stearic acid 8.0g
Squalane 10.0g
Self-emulsifying type propylene glycol monostearate 3.0g
Polyoxyethylene cetyl ether 1.0g
Spices 0.5g
Sanitas is an amount of
Oxidation inhibitor is an amount of
Propylene glycol 7.8g
Glycerine 4.0g
Hyaluronate sodium 0.15g
Compound (1) 0.05g
Trolamine 1.0g
Purified Water 57.5g
Embodiment 11: the Production Example of shampoo
Use following material, according to the usual method manufacturing.
Sodium alkylether sulphate 16.0g
Lauric acid diethyl amide 4.0g
Propylene glycol 1.95g
Sanitas, pigment, spices are an amount of
Oxidation inhibitor is an amount of
Compound (1) 0.05g
Purified Water 78.0g
As mentioned above, find that according to the present invention derivative or its salt of the novel flavone C glycoside that contains in the oolong tea has significant anti-allergic effects, can provide with them is medical composition, the food compositions of effective constituent or the material of making up.

Claims (10)

1. the flavone C glycoside derivatives shown in the formula (1) or its salt.
2. the flavone C glycoside derivatives shown in the formula (2) or its salt.
Figure C038181060002C2
3. preventing and/or treating of anaphylactic disease used medical composition, and it contains claim 1 or 2 described flavone C glycoside derivatives or its salt at least a kind.
4. the described medical composition of claim 3, wherein, this anaphylactic disease is at least a disease that is selected from atopic dermatitis, contact dermatitis, pollinosis.
5. food compositions, its at least a kind of containing claim 1 or 2 described flavone C glycoside derivatives or its salt is as the antiallergic property composition.
6. the described food compositions of claim 5, it is the form with beverage.
7. the described food compositions of claim 5, wherein, this food compositions is cake class, wheaten food class, soyabean processing product, milk-product, egg processed goods, the flesh of fish is blended prepared food, grease or the food flavouring that adds other material and make.
8. make up and expect that its at least a kind of containing claim 1 or 2 described flavone C glycoside derivatives or its salt is as the antiallergic property composition.
9. the described cosmetic material of claim 8, wherein, this material of making up is skin care product, makeup, hair cosmetics or bathing material.
10. at least a kind of claim 1 or 2 described flavone C glycoside derivatives or its salt use in the manufacturing of the medical composition with antiallergic property effect, food compositions or the material of making up.
CNB038181061A 2002-07-03 2003-07-03 Novel derivative of flavone c-glycoside and composition containing the same Expired - Fee Related CN1313469C (en)

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JP2005289888A (en) * 2004-03-31 2005-10-20 Suntory Ltd Preparation method of flavone c glycoside derivative
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JP2006342103A (en) * 2005-06-09 2006-12-21 National Cancer Center-Japan Carcinogenesis inhibitor having oolong tea leaf extract otac as active ingredient
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JP5214226B2 (en) * 2007-11-02 2013-06-19 株式会社 資生堂 Chafroside-rich tea leaves and method for producing the same
EP2385049A4 (en) * 2009-01-03 2012-08-08 Shizuoka Prefecture Public University Corp Sulfated c-glycoside, method for isolating same and method for synthesizing same
EP2359698B1 (en) * 2010-01-22 2013-12-04 Symrise AG Compositions with a surfactant system comprising saponins, and lecithin
JP2012219076A (en) * 2011-04-12 2012-11-12 Shizuokaken Koritsu Daigaku Hojin Skin-whitening agent and melanogenesis inhibitor
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CN109157465B (en) * 2018-08-08 2020-11-13 浙江大学 High-purity bamboo leaf carbon glycoside flavone nano particle, preparation method and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03157330A (en) * 1989-11-13 1991-07-05 Itouen:Kk Antiallergic agent
JPH1077231A (en) * 1996-07-12 1998-03-24 Suntory Ltd Antiallergic agent
EP0853943A1 (en) * 1996-12-19 1998-07-22 Suntory Limited Antiallergic agent

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2077703T3 (en) * 1990-03-30 1995-12-01 Suntory Ltd GLUCOSILTRANSFERASE INHIBITORS, AS WELL AS METHODS FOR THE PREVENTION OF DENTAL CARIES AND ANTI-CARIES FOODS USED BY THESE INHIBITORS.
JP2006176407A (en) * 2003-04-18 2006-07-06 Daiichi Asubio Pharma Co Ltd New flavone derivative, method for producing the same and medicine composition containing the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03157330A (en) * 1989-11-13 1991-07-05 Itouen:Kk Antiallergic agent
JPH1077231A (en) * 1996-07-12 1998-03-24 Suntory Ltd Antiallergic agent
EP0853943A1 (en) * 1996-12-19 1998-07-22 Suntory Limited Antiallergic agent

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
'A new convenient synthesis of benzofuroflavones' AHLUWALIA V.K. ET AL,INDIAN JOURNAL OF CHEMIS TRY,Vol.26B No.3 1987 *
'Claisen rearrangement of 7-prenyl ethers of chrysin &3-0-methylgalangin: a novel 3-0-demethylation' JAIN A.C. ET AL,INDIAN JOURNAL OF CHEMISTRY,Vol.11 No.8 1973 *
Fuether prenylflavonoids from artocarpus elasticus. Kijjoa,A. et al,Phytochemistry,Vol.47 No.5 1998 *

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